title: Activation of cardiomyocytes depending on their proximity to human bone marrow stem cells.
abstract: Our study aimed to elucidate whether bone marrow stem cell (BMC) treatment might result in a cellular response in cardiomyocytes IN VITRO. Subconfluent neonatal rat cardiomyocyte cultures were cocultured for three days with Vybrant CM-DiI labeled BMC from human sternal bone marrow and underwent immunohistological staining for the proto-oncogene c-Myc and the cell cycle proteins CDK2, CDK4 and ATF-3. β-adrenoceptor density was analyzed using [125I]-iodocyanopindolol (ICYP) histoautoradiography. Quantitative analysis of immunohistochemical images revealed significantly increased expression and upregulation of c-Myc, and its downstream targets ATF-3, CDK2 and CDK4 in neighboring cardiomyocytes to BMC, depending on their distance to the BMC compared to cardiomyocytes far from the BMC. Histoautoradiography revealed a significantly higher β-adrenoceptor density in cardiomyocytes in the immediate vicinity to the BMC. With increasing distance to the BMC, β-adrenoceptor density in cardiomyocytes declined. Thus, a small number of BMC can affect a larger number of cardiomyocytes by activating an intracellular signaling cascade and enhancing β-adrenoceptor density.
authors.affiliation: Clinic for Cardiac Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Roeske
authors.forename: A
authors.initials: A
authors.lastname: Stein
authors.forename: A
authors.initials: A
authors.lastname: Salameh
authors.forename: A
authors.initials: A
authors.lastname: Rastan
authors.forename: B
authors.initials: B
authors.lastname: Ziegelhoeffer
authors.forename: J
authors.initials: J
authors.lastname: Garbade
authors.forename: M
authors.initials: M
authors.lastname: Misfeld
authors.forename: M
authors.initials: M
authors.lastname: Kostelka
authors.forename: F W
authors.initials: FW
authors.lastname: Mohr
authors.forename: S
authors.initials: S
authors.lastname: Dhein
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001854:Bone Marrow Cells / Q000378:metabolism*; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D011943:Receptors, Adrenergic, beta; C495892:Cdk2 protein, rat; C495903:Cdk4 protein, rat; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4